Central resistin overexposure induces insulin resistance through Toll-like receptor 4. Diabetes 2013, 62, 102–114. [CrossRef] [PubMed

Resistin promotes both inflammation and insulin resistance associated with energy homeostasis impairment. However, the resistin receptor and the molecular mechanisms mediating its effects in the hypothalamus, crucial for energy homeostasis control, and key insulin-sensitive tissues are still unknown. In the current study, we report that chronic resistin infusion in the lateral cerebral ventricle of normal rats markedly affects both hypothalamic and peripheral insulin responsiveness. Central resistin treatment inhibited insulin-dependent phosphorylation of insulin receptor (IR), AKT, and extracellular signal–related kinase 1/2 associated with reduced IR expression and with upregulation of suppressor of cytokine signaling-3 and phosphotyrosine phos-phatase 1B, two negative regulators of insulin signaling. Addition-ally, central resistin promotes the activation of the serine kinases Jun NH2-terminal kinase and p38 mitogen-activated protein kinase